3-氟吡啶-2-甲醇 | 31181-79-0

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 3-氟吡啶-2-甲醇
• 中文别名: 3-氟-2-吡啶甲醇
• 英文名称: (3-fluoropyridin-2-yl)methanol
• 英文别名: (3-fluoro-2-pyridyl) methanol
• CAS: 31181-79-0
• 化学式: C₆H₆FNO
• 分子量: 127.118
• InChiKey: FKTCIWBKNWUDAX-UHFFFAOYSA-N

物化性质

• 沸点：
  194.3±25.0 °C(Predicted)
• 密度：
  1.262±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 安全说明：
  S23,S26,S36/37/39
• 危险类别码：
  R20/21/22,R36/37/38
• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (3-Fluoropyridin-2-yl)methanol
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: (3-Fluoropyridin-2-yl)methanol
CAS number: 31181-79-0

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C6H6FNO
Molecular weight: 127.1

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen fluoride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

应用

3-氟吡啶-2-甲醇是一种医药中间体，可用于合成具有多种用途的化合物。例如，它可以用作原料来合成一种四氢咔唑衍生物，该衍生物可用作雄激素受体调节剂。其结构如下：

具体合成步骤为：将215 mg（1.69 mmol）3-氟吡啶-2-甲醇溶解在10 mL二氯甲烷中，并冷却至0℃。然后加入亚硫酰氯（160 μL，2.20 mmol），搅拌1小时后，再加入50 mL二氯甲烷。随后将反应物与饱和碳酸氢钠水溶液（2×40 mL）和盐水（2×40 mL）进行搅拌。分离并用硫酸镁干燥有机部分，过滤，在减压下浓缩，得到2-氯甲基-3-氟吡啶。

接下来，将60%的氢化钠80 mg（1.99 mmol）混悬在2 mL DMF中，并冷却至0℃。通过注射器缓慢加入N-(6-氰基-2,3,4,9-四氢-1H-咔唑-3-基)-异丁酰胺（253 mg，0.90 mmol）的DMF溶液（2 mL），搅拌30分钟后升温至室温达60分钟。加入180 mg（0.99 mmol）2-氯甲基-5-氟吡啶盐酸盐并搅拌反应物约12小时。用饱和氯化铵水溶液（5 mL）淬灭反应，然后依次用乙酸乙酯（50 mL）、水（50 mL）和盐水（2×50 mL）洗涤溶液。分离有机相后经硫酸镁干燥、过滤，并在减压下蒸发。最后将所得残余物用10 mL乙醚研磨5分钟，过滤得到187 mg（53%）的化合物，为浅黄色固体。

反应信息

• 作为反应物：
  描述：

  3-氟吡啶-2-甲醇 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-氯甲基-3-氟吡啶
  参考文献：
  名称：

  2-[（（2-吡啶基甲基）亚磺酰基] -1H-噻吩并[3,4-d]咪唑。一类新型的胃H + / K（+）-ATPase抑制剂。

  摘要：

  合成2-[（（2-吡啶基甲基）亚磺酰基]噻吩并咪唑类化合物，并研究其作为胃H + / K（+）-ATPase的潜在抑制剂。已发现两种可能的噻吩并咪唑系列的[3,4-d]异构体在体外和体内都是有效的胃酸分泌抑制剂。结构活性关系表明，特别是在吡啶部分的4位具有额外的电子要求特性的亲脂性烷氧基，苄氧基和苯氧基取代基与未取代的噻吩并[3,4-d]咪唑结合会导致具有高活性的化合物。良好的化学稳定性。噻吩并[3,4-d]咪唑部分的各种取代方式导致较低的生物活性。选择了七氟丁氧基衍生物萨维拉唑（HOE 731，5d）进行进一步开发，目前正在临床评估中。

  DOI：

  10.1021/jm00081a004
• 作为产物：
  描述：

  2,3-吡啶二羧酸酐 在 sodium tetrahydroborate 、 pyridine hydrofluoride 、 叠氮磷酸二苯酯 、 三乙胺 、 calcium chloride 、 sodium nitrite 作用下， 以 甲醇 、 叔丁醇 为溶剂， 反应 49.17h， 生成 3-氟吡啶-2-甲醇
  参考文献：
  名称：

  3-氟吡啶-2-甲醇的一种新合成方法

  摘要：

  本发明涉及化合物制备领域，具体地，涉及3‑氟吡啶‑2‑甲醇的一种新合成方法。3‑氟吡啶‑2‑甲醇具有式V所示结构，本发明以价格低廉的喹啉酸为起始原料，通过酸酐化、酯化、氨化、氨基氟化、酯基还原等步骤，得到目标产物3‑氟吡啶‑2‑甲醇，其结构经1HNMR和13CNMR表征。这是一种全新的3‑氟吡啶‑2‑甲醇的合成方法，该方法成本低廉，工艺简单，收率高，质量好，具有较高的工业化价值。

  公开号：

  CN111004171A

文献信息

• [EN] TRIAZOLOPYRIDINE AND TRIAZOLOPYRIMIDINE INHIBITORS OF MYELOPEROXIDASE<br/>[FR] INHIBITEURS DE MYÉLOPEROXYDASE DE TYPE TRIAZOLOPYRIDINE ET TRIAZOLOPYRIMIDINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016040417A1

  公开（公告）日：2016-03-17

  The present invention provides compounds of Formula (I): wherein A and R1 are each as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and/or eosinophil peroxidase (EPX) inhibitors, which may be used as medicaments.

  本发明提供了式（I）的化合物：其中A和R1如规范中所定义，并包括任何此类新化合物的组合物。这些化合物是髓过氧化物酶（MPO）抑制剂和/或嗜酸性粒细胞过氧化物酶（EPX）抑制剂，可用作药物。
• RADIOLABELLED PDE10 LIGANDS
  申请人：Andrés-Gil José Ignacio

  公开号：US20120213703A1

  公开（公告）日：2012-08-23

  The present invention relates to novel, selective, radiolabelled PDE10 ligands which are useful for imaging and quantifying the PDE10A enzyme in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo.

  本发明涉及新型的、选择性的、放射性标记的PDE10配体，这些配体可用于通过正电子发射断层扫描（PET）对组织中的PDE10A酶进行成像和定量。该发明还涉及包含这些化合物的组合物、制备这些化合物和组合物的方法，以及将这些化合物和组合物用于在体外或体内成像组织、细胞或宿主的应用。
• Synthesis, In Vivo Occupancy, and Radiolabeling of Potent Phosphodiesterase Subtype-10 Inhibitors as Candidates for Positron Emission Tomography Imaging
  作者：José-Ignacio Andrés、Meri De Angelis、Jesús Alcázar、Laura Iturrino、Xavier Langlois、Stefanie Dedeurwaerdere、Ilse Lenaerts、Greet Vanhoof、Sofie Celen、Guy Bormans

  DOI：10.1021/jm200536d

  日期：2011.8.25

  for in vivo imaging using positron emission tomography (PET). We now describe the synthesis and biological evaluation of a series of related pyridinyl analogues that exhibit high potency and selectivity as PDE10A inhibitors. The most interesting compounds were injected in rats to measure their levels of PDE10A occupancy through an in vivo occupancy assay. The 3,5-dimethylpyridine derivative 3 and the

  我们最近报道了磷酸二酯酶10A（PDE10A）抑制剂2- [4- [1-（2- [ 18 [ ] F]氟乙基）-4-吡啶-4-4-基-1 H-吡唑-3-基]-苯氧基甲基]-喹啉（[ 18 F] 1a）是使用正电子发射断层扫描（PET）进行体内成像的有前途的候选物。现在，我们描述了一系列相关的吡啶基类似物的合成和生物学评估，这些吡啶基类似物作为PDE10A抑制剂具有很高的效力和选择性。将最有趣的化合物注射到大鼠中，以通过体内占有率测定法测量其PDE10A占有率水平。3,5-二甲基吡啶衍生物3和5-甲氧基吡啶衍生物4的可比性与1a。因为这些衍生物显示出较低的体外活性，并且比1a的亲脂性略低，所以我们假设它们可以表现为更好的PET成像配体。放射性合成化合物[ 18 F] 3，[ 18 F] 4和[ 11 C] 4并在大鼠中进行生物分布研究，作为在脑中对PDE10A进行体内成像的候选PET放射性配体进行初步评估。
• [EN] 2,4-DIOXO-QUINAZOLINE-6-SULFONAMIDE DERIVATIVES AS INHIBITORS OF PARG<br/>[FR] DÉRIVÉS DE 2,4-DIOXO-QUINAZOLINE-6-SULFONAMIDE EN TANT QU'INHIBITEURS DE LA PARG
  申请人：CANCER REC TECH LTD

  公开号：WO2016092326A1

  公开（公告）日：2016-06-16

  The present invention relates to compounds of formula I that function as inhibitors of PARG (Poly ADP-ribose glycohydrolase) enzyme activity wherein R1a, R1b, R1c, R1d, R1e, W, X1, X2, X3, X4, X5, X6, X7, c are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which PARG activity is implicated.

  本发明涉及作为PARG（Poly ADP-ribose glycohydrolase）酶活性抑制剂的I式化合物，其中R1a、R1b、R1c、R1d、R1e、W、X1、X2、X3、X4、X5、X6、X7、c如本文所定义。本发明还涉及制备这些化合物的方法，包括含有它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及其他涉及PARG活性的疾病或症状中的用途。
• [EN] 2-SUBSTITUTED QUINAZOLINE COMPOUNDS COMPRISING A SUBSTITUTED HETEROCYCLIC GROUP AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS QUINAZOLINE SUBSTITUÉS EN POSITION 2 COMPRENANT UN GROUPE HÉTÉROCYCLIQUE SUBSTITUÉ ET LEUR MÉTHODE D'UTILISATION
  申请人：ARAXES PHARMA LLC

  公开号：WO2017087528A1

  公开（公告）日：2017-05-26

  Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): (I) or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5a, R5b, R6, A, G1, G2, L1, L2, m1, m2, n, X and E are as defined herein, and wherein at least one of R3a, R3b, R4a or R4b is not H. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

  提供了作为G12C突变KRAS蛋白抑制剂活性的化合物。这些化合物具有以下结构（I）：（I）或其药学上可接受的盐、立体异构体或前药，其中R1、R2a、R2b、R2c、R3a、R3b、R4a、R4b、R5a、R5b、R6、A、G1、G2、L1、L2、m1、m2、n、X和E如本文所定义，并且其中至少一个R3a、R3b、R4a或R4b不是H。还提供了与制备和使用这些化合物相关的方法，包括包含这些化合物的药物组合物以及调节G12C突变KRAS蛋白活性以治疗癌症等疾病的方法。